P372: CMV REACTIVATIONS/INFECTIONS IN PH+ ALL PATIENTS TREATED WITH DASATINIB WITH OR WITHOUT BLINATUMOMAB. A RETROSPECTIVE MULTICENTER CAMPUS ALL STUDY
Authors: Mario Annunziata, Monia Lunghi, Fabio Giglio, Matteo Leoncin, Michelina Dargenio, Massimiliano Bonifacio, Marco De Gobbi, Carla Mazzone, Roberta Agrippino, Davide Lazzarotto, Elisa Roncoroni, Marzia Defina, Nicola Fracchiolla, Fabio Guolo, Maria Ilaria Del Principe, Barbara Scappini, Antonino Mulè, Maria Ciccone, Crescenza Pasciolla, Felicetto Ferrara, Giovanni Pizzolo, Robin Foà, Sabina Chiaretti
Journal: HemaSphere (2023)

Background: CMV reactivation can occur after immunosuppression, in particular in the transplant, but it rarely occurs during chemotherapy for hematologic malignancies. Novel targeted compounds has raised the issue of CMV infections. Sporadic case of CMV infection have been reported during dasatinib treatment of ALL. The incidence of CMV infection has been observed in about 10% of patients treated frontline with dasatinib followed by blinatumomab (Foà et al, NEJM 2020). Aims: The aim of this work was to analyze the incidence of CMV reactivation/infection, and the management and outcome of patients treated frontline either with the combination of dasatinib and blinatumomab (Group 1) or with dasatinib alone (Group 2) Methods: Within the Campus ALL network, we have retrospectively collected 141 adult Ph+ ALL patients, diagnosed between April 2008 and February 2022 in 19 Italian hematologic centers. To define a CMV reactivation and disease, we employed the ECIL7 criteria (Lancet Infect Dis 2019). Quantitative CMV DNA PCR was performed using RT CMV assay Results: Among the 141 patients included in the current study, 41 (29%) developed a CMV infection or reactivation, 24 (58.5%) of whom belonging to Group 1 and 17 (41.5%) to Group 2. The main features of this population are summarized in Table 1. Overall, 73 episodes of CMV infection were reported, 51 in Group 1 and 22 in Group 2 patients (p: 0.003). The median number of episodes was 2 and 1 for Groups 1 and 2, respectively. We found no statistically significant differences in terms of CMV reactivation without symptoms between the two groups (58% vs 42%); contrarywise, CMV disease was more frequent in Group 1 than in Group 2 patients (80% vs 20%; p 0.037). The median time between diagnosis and first episode of CMV infection (either reactivation or disease) was 4 and 9 months in Group 1 and 2, respectively. Interestingly, hypogammaglobulinemia was significantly more frequent in patients belonging to Group 1 compared Group 2 patients (58% vs 19%; p 0.003), in line with the known effect of blinatumomab. In patients with CMV disease, the most frequent manifestations were cytopenia (33%), fever (29%), diarrhea (31%), all occurring with variable degree; rare episodes of rash, bone pain and pneumonia were also recorded. Valganciclovir was the most frequently used antiviral (72% of cases), without difference between the two Groups, nor between the reactivation and disease status. The remaining antiviral therapy administered consisted in ganciclovir, acyclovir and foscarnet in 17%, 9% and 2% of patients, respectively. The median therapy duration was 21 days (range 14-180) in Group 1 and 25 days (range 14-60) in Group 2. Upon antiviral therapy discontinuation, a persistent viral load was reported in 21.6% of Group 1 patients and in 4.4% of Group 2 patients. Infusion of immunoglobulins was added to the antiviral therapy only in 3 patients with symptomatic CMV disease. 13% of patients in both Groups were treated as inpatient, primarily due to logistic reasons whereas hospitalizations for symptoms’ severity were rare. Summary/Conclusion: The incidence of CMV reactivation/infection is relatively frequent in adult Ph+ ALL patients treated with dasatinib-based regimens. While we found no differences in the incidence of reactivation between patients receiving dasatinib-blinatumomab or dasatinib, CMV disease was significantly more frequent in patients treated with dasatinib in association with blinatumomab. Furthermore, a status of hypogammaglobulinemia was significantly higher in patients receiving the combination of dasatinib plus blinatumomab. Finally, no patient died of CMV-related complications in both armsKeywords: Acute lymphoblastic leukemia, CMV infection